CD4/CD8 Double-negative T-cell Lymphoma: A Variant of Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-cell Lymphoma?

Miyauchi, Takashi; Abe, Riichiro; Morita, Yusuke; Adachi, Mitsuru; Shiba, K.; Hamade, Yohei; Saito, Nagahito; Nishimura, Machiko; Ibata, Makoto; Okada, Ken-ichi; Shigematsu, Akio; Endo, Tomoyuki; Kawai, Kazuhiro; Teshima, T.; Shimizu, Hiroshi

doi:10.2340/00015555-2102

Cited by 7 publications

(6 citation statements)

References 4 publications

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“…More recently, Miyauchi et al. reported a case of DN CTCL with clinical and pathological characteristics similar to those of primary cutaneous CD8 + CTCL, characterized by TCRβ positivity and expression of granzyme B, perforin and cytotoxic marker TIA-1 ( 97 ). Additionally, Beltran et al.…”

Section: The Warrior and Culprit In Cancer Developmentmentioning

confidence: 94%

CD3+CD4-CD8- (Double-Negative) T Cells in Inflammation, Immune Disorders and Cancer

et al. 2022

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The crucial role of CD4+ and CD8+ T cells in shaping and controlling immune responses during immune disease and cancer development has been well established and used to achieve marked clinical benefits. CD3+CD4-CD8- double-negative (DN) T cells, although constituting a rare subset of peripheral T cells, are gaining interest for their roles in inflammation, immune disease and cancer. Herein, we comprehensively review the origin, distribution and functions of this unique T cell subgroup. First, we focused on characterizing multifunctional DN T cells in various immune responses. DN regulatory T cells have the capacity to prevent graft-versus-host disease and have therapeutic value for autoimmune disease. T helper-like DN T cells protect against or promote inflammation and virus infection depending on the specific settings and promote certain autoimmune disease. Notably, we clarified the role of DN tumor-infiltrating lymphocytes and outlined the potential for malignant proliferation of DN T cells. Finally, we reviewed the recent advances in the applications of DN T cell-based therapy for cancer. In conclusion, a better understanding of the heterogeneity and functions of DN T cells may help to develop DN T cells as a potential therapeutic tool for inflammation, immune disorders and cancer.

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Section: The Warrior and Culprit In Cancer Developmentmentioning

confidence: 94%

CD3+CD4-CD8- (Double-Negative) T Cells in Inflammation, Immune Disorders and Cancer

et al. 2022

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“…Importantly, the long-lived CAR T cells did not show aggressive expansion capability but did have active T lymphocyte functionality, presumably serving a tumor immune surveillance function. Alternatively, given that DN T lymphoma cells were reported in several cases with mycosis fungoides [ 29 , 30 ], a possible malignant transformation of the persisting CAR T cells remains a risk that cannot be completely ignored and requires close watching.…”

Section: Discussionmentioning

confidence: 99%

Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial

Xu,

Wang,

et al. 2024

J Hematol Oncol

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Background The autologous anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M has been approved for the treatment of relapsed and refractory multiple myeloma in many countries across the world under the name ciltacabtagene autoleucel. LEGEND-2 was the first-in-human trial of LCAR-B38M and yielded deep and durable therapeutic responses. Here, we reported the outcomes in LEGEND-2 after a minimal 5-year follow-up. Methods Participants received an average dose of 0.5 × 106 cells/kg LCAR-B38M in split or single unfractionated infusions after cyclophosphamide-based lymphodepletion therapy. Investigator-assessed response, survival, safety and pharmacokinetics were evaluated. Results Seventy-four participants enrolled and had a median follow-up of 65.4 months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 21.0% and 49.1%, with progressive flattening of the survival curves over time. Patients with complete response (CR) had longer PFS and OS, with 5-year rates of 28.4% and 65.7%, respectively. Twelve patients (16.2%) remained relapse-free irrespective of baseline high-risk cytogenetic abnormality and all had normal humoral immunity reconstituted. An ongoing CR closely correlated with several prognostic baseline indices including favorable performance status, immunoglobulin G subtype, and absence of extramedullary disease, as well as a combination cyclophosphamide and fludarabine preconditioning strategy. Sixty-two (83.8%) suffered progressive disease (PD) and/or death; however, 61.1% of PD patients could well respond to subsequent therapies, among which, the proteasome inhibitor-based regimens benefited the most. Concerning the safety, hematologic and hepatic function recovery were not significantly different between non-PD and PD/Death groups. A low rate of second primary malignancy (5.4%) and no severe virus infection were observed. The patients who tested positive for COVID-19 merely presented self-limiting symptoms. In addition, a sustainable CAR T population of one case with persistent remission was delineated, which was enriched with indolently proliferative and lowly cytotoxic CD4/CD8 double-negative functional T lymphocytes. Conclusions These data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma. Trial registration LEGEND-2 was registered under the trial numbers NCT03090659, ChiCTRONH-17012285.

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“…and is not included in the revised fourth edition of the World Health Organization (WHO) classification of Tumors of Hematopoietic and Lymphoid Tissues. 1,2 CD4/8-DN TCL would be categorized in the "primary cutaneous peripheral T-cell lymphoma, NOS (not otherwise specified)" section of the WHO classification. The treatment of CD4/8-DN TCL has not been established.…”

mentioning

confidence: 99%

“…The treatment of CD4/8-DN TCL has not been established. 1,2 Here, we present a case of CD4/8-DN TCL that responded to combination therapy of bexarotene and total skin electron beam therapy (TSEBT).…”

mentioning

confidence: 99%

“…CD4/8-DN TCL remains challenging to diagnose because it is not classified in the current TCL classification. 1,2 CD4/8-DN TCL has been reported in various forms, including variants of mycosis fungoides or primary cutaneous CD8+ aggressive epidermotropic cytotoxic TCL. 1,2 Future accumulation and evaluation of patients are necessary to evaluate the independence of the CD4/8-DN TCL.…”

mentioning

confidence: 99%

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CD4/CD8 double‐negative T‐cell lymphoma successfully treated with a combination of bexarotene and total skin electron beam therapy

Tanigawa

Fukumoto

Imamura

et al. 2023

The Journal of Dermatology

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CD4/CD8 Double-negative T-cell Lymphoma: A Variant of Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-cell Lymphoma?

Cited by 7 publications

References 4 publications

CD3+CD4-CD8- (Double-Negative) T Cells in Inflammation, Immune Disorders and Cancer

CD3+CD4-CD8- (Double-Negative) T Cells in Inflammation, Immune Disorders and Cancer

Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial

CD4/CD8 double‐negative T‐cell lymphoma successfully treated with a combination of bexarotene and total skin electron beam therapy

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